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Melanie Ehrlich


Melanie Ehrlich

Melanie Ehrlich, PhD

Professor, Hayward Human Genetics Center, Tulane Cancer Center, and Center for Bioinformatics and Genomics

Research Interests:
Epigenetics in normal development and disease

We have been studying epigenetics since the 1970’s. In collaboration with Charles Gehrke, we published the first study demonstrating tissue-specific differences in the levels of DNA methylation in humans. In 1983, our lab and, independently, the lab of Bert Vogelstein were the first to publish that there are abnormalities in DNA methylation in human cancers. Later, we were the first to report very frequent hypomethylation of highly repeated DNA sequences in human cancers. Our findings on genome-wide, cancer-associated DNA hypomethylation have been confirmed by numerous laboratories. 

Our interest in how certain transcription factors might distinguish between methylated and nonmethylated DNA recognition sites led to the first report of a vertebrate DNA-binding protein with specificity for DNA methylation (MDBP/RFX). Alongside our many studies of this protein, we continued analyzing aberrant DNA hypermethylation vs. hypomethylation in human cancer, e.g., and the relationships between cancer-associated DNA hypomethylation and pericentromeric chromosome rearrangements. We also investigated this relationship in normal chorionic villus cultures. As a follow-up to studying the associations between DNA hypomethylation and chromosomal rearrangements, we studied a rare DNA methyltransferase deficiency (immunodeficiency, centromeric region instability, facial anomalies, ICF) in which there are bizarre diagnostic rearrangements of hypomethylated satellite DNA in the pericentromic regions of chromosomes 1 and 16.

Results from our research on additional targets of abnormal DNA hypomethylation in the ICF syndrome converged with our earlier findings of sequences displaying gamete-associated DNA hypomethylation. One of the most interesting sequences that we found to display hypomethylation in ICF cells was a macrosatellite repeat sequence (D4Z4) that is associated with a very unusual type of dominant muscular dystrophy (facioscaulohumeral muscular dystrophy, FSHD). D4Z4 is very similar to a sequence with sperm-specific DNA hypomethylation that we had previously cloned.

We profiled genome-wide expression in myoblasts and myotubes from controls and FSHD patients to better understand normal and aberrant muscle formation. In that study we uncovered the first convincing evidence for generalized dysregulation of gene expression in this disease. Our study indicates the underappreciated complexity of the role of D4Z4 hypomethylation in FSHD. To better understand transcription control in FSHD and normal myoblasts and myotubes, we have used these cells to investigate the role of genome-wide epigenetic changes associated with myogenesis. This line of research includes use of ENCODE whole-genome profiles of human DNA methylation and open chromatin (DNasel hypersensitive sites) from these myogenic progenitor cells and from dozens of different types of normal non-muscle samples. Among the genes we recently studied for tissue-specific epigenetics were the differention-linked HOX genes. These studies provided new insights into the breadth of roles that can be played by differential DNA methylation in control of gene expression. Moreover, we showed an unexpected enrichment of the newly recognized sixth base of human DNA (5-hydroxymethylcytosine) in skeletal muscle overall and in certain gene regions in particular in comparison to many other tissue types and to progenitor muscle cells.

Our research on development-linked epigenetics, including tissue-specific differences genomic 5-methylcytosine and 5-hydroxymethylcytosine is continuing. We found that many genes in a very important developmental signaling pathway, the Notch pathway, display specific peaks of these two bases in muscle cell precursors (myoblasts and myotubes), skeletal muscle, heart muscle, and brain (cerebellum). The peaks of these two specifically modified bases were present inside the genes as well as rather far from the genes in intergenic regions. The DNA epigenetics and chromatin epigenetics significantly associated with the skeletal muscle cell lineage in and around Notch genes as well as muscle-associated chromatin epigenetics leads to new understanding of how the Notch signaling pathway is likely to work in muscle progenitor cells and adult muscle tissue. We are continuing our studies of the biological role of skeletal muscle-associated differences in DNA modification (both 5-methylcytosine and 5-hydroxymethylcytosine) and chromatin modification.

In addition, to our current emphasis on normal tissue-specific epigenetics (DNA methylation, open chromatin, and histone modifications), we are involved in a collaborative study with Garth Rauscher on the relationship between DNA methylation marks in breast cancer and racial disparities in disease outcome.

Melanie Ehrlich Curriculum Vitae
Melanie Ehrlich Publications

Other Affiliations:

Tulane Cancer Center (core member):
http://tulane.edu/som/cancer/research/people/melanie-ehrlich.cfm

Tulane Center for Bioinformatics and Genomics (core member):
http://tulane.edu/publichealth/bio/epigenetics-of-muscle-formation.cfm 

 

Contact:
Melanie Ehrlich, Ph.D.
Hayward Genetics Center and Tulane Cancer Center
1430 Tulane Avenue, SL-31
New Orleans, LA 70112
(504)988-2449
ehrlich@tulane.edu

 

1430 Tulane Ave, New Orleans, LA 70112 504-988-5263 medsch@tulane.edu